Immunotherapy Is The Most Promising Cancer Treatment — So Why Can’t More People Access It?
It’s curing previously incurable cancers (like Stage IV Melanoma) and offering hope to patients who previously were handed death sentences. If you or a loved one has cancer, you may have heard of this incredible treatment that uses the body’s own immune system to fight and kill cancer cells … it’s called IMMUNOTHERAPY.
But despite its popularity in the media and scientific literature, many cancer patients may not know if immunotherapy is available to them or have the resources to access it.
Indeed, according to a 2019 study published in JAMA, while US patients with cancer who are eligible for checkpoint inhibitor drugs (a major class of immunotherapy drugs) increased from 1.5% in 2011 to 43.6% in 2018, the percentage of patients estimated to respond to those drugs only sat around 12.4% in 2018 (source PMID: 31050774).
Thus, immunotherapy isn’t as available or ubiquitous in cancer care as we might think. And the number of patients who may respond to these drugs is modest at best.
So let’s talk about what immunotherapy is, how to find out if you qualify, and WHO exactly pays for it.
What Is Immunotherapy?
Immunotherapies are drugs designed to use the body’s own immune system to fight cancer (vs drugs like chemotherapy and radiation that act more like poison to both cancerous and regular cells). The most often used immunotherapy drugs are Checkpoint Inhibitors. However, there are other types of immunotherapy drugs like CAR T-Cell Therapy and Cancer Vaccines.
But let’s talk about checkpoint inhibitors. These drugs “take the brakes off the immune system” and allow it to once again “see” cancer cells and attack them.
Essentially, cancer cells have evolved methods (via mutations or overexpression of certain proteins) to hide from the immune system.
Let’s get a little sciencey and look at an example using PD1, a protein on T-cells (a type of immune cell) that binds to a protein on normal cells called PD-L1, like two cells shaking hands. When this hand-shake happens that normal cell is telling the T-cell (which kills bad guys) to leave it alone.
Well, cancer cells can express PD-L1 as well, or even OVER express it. In fact, when cancer cells do this, they are telling YOUR immune system “Hey, nothing to see here. I’m just a normal cell. Wink wink.” The T-cell registers that message and doesn’t attack.
Immunotherapy drugs BLOCK this from happening. They INHIBIT this pathway, the handshake never happens, and the cancer cell can’t relay that message. Since no proteins are telling the T-cell not to attack, it can NOW see the cancer cell and target it for destruction.
These drugs are very effective at doing this in certain circumstances.
But they need a TARGET … like a PD-1 or PD-L1 to work off of (or in the case of other immunotherapy drugs, CTLA-4 or LAG-3).
Oncologists use genomic testing or immunohistochemistry testing (IHC) to look for those proteins or biomarkers and determine WHAT if any targets are there, and which drugs can be used. So let’s see how you qualify for this.
Who Qualifies for Immunotherapy?
The moment you get diagnosed with cancer you may ask your doctor, “Give me that immunotherapy everyone is talking about!”
It’s known to have fewer side effects than chemotherapy and radiation and kills cancer cells with more precision. But as stated before less than half of all cancer patients QUALIFY (based on their biomarkers and diagnosis) for checkpoint inhibitors and less than 15% may see a response to these drugs. Why?
According to The Cancer Research Institute, the FDA has only approved immunotherapies for 20 or so cancers with specific genetic mutations (though the number continues to grow). Which means many cancers may not be approved.
You’ll need to ask your oncologist for full genomic sequencing (which can be pricey) or immunohistochemistry testing (IHC), which is less comprehensive, but more accessible. Once they analyze specific biomarkers, like PD-L1 expression, Microsatellite instability-high (MSI-H), or Tumor mutational burden (TMB), they can determine whether or not an immunotherapy drug is right for you. Sometimes these tests are covered by insurance, sometimes they are not.
So what if you have the right biomarkers, and your oncologist thinks you’re a good candidate, BUT your cancer hasn’t made the approved list yet?
“If an immunotherapy or other drug is not approved, options do become a bit more limited and/or expensive, as insurance will often not cover the drug,” explains Dr. Peter Fecci, MD, Director of Brain Tumor Immunotherapy Program and the Center for Brain and Spine Metastasis at Duke University, to me via email.
“However, if a drug has not been approved, that usually means it is still under investigation, in which case there are likely clinical trials available testing the drug,” he added.
Indeed, if this happens to you, your doctor may need to use the immunotherapy drug off-label, which is a common practice in oncology, but can be cost-prohibitive if it’s ultimately not covered by insurance.
For example, KEYTRUDA, a well-known PD-1 inhibitor has a list price of almost $175,000 per year. This drug, made by Merck, generates ~$17 billion per year and its patent doesn’t expire until 2028.
If off-label is not an option, you may need to look for a clinical trial that offers the drug for your cancer type. Qualifying for clinical trials can be confusing and difficult and they come with rules of their own (like no additional therapies or complementary therapies allowed).
“Clinical trials are designed to answer specific scientific questions about patient responses to Treatment,” explains Jill O’Donnell-Tormey, PHD and CEO and Director of Scientific Affairs, at the Cancer Research Institute. “Scientists must reduce the number of variables involved to arrive at the clearest determination of the treatment’s effect.”
Clinical trial design can be frustrating to cancer patients who often need drugs in their bodies now. But as O’Donnell-Tormey points out, they’re designed that way to truly gauge the effectiveness of the drug. “CRI’s website also features a free Immunotherapy Clinical Trial Finder service at cancerresearch.org/cancer-clinical-trials,” she says.
So Who Pays For It?
As mentioned before, if your cancer is not on the approved list, your oncologist can use the drug off-label. This just means using the drug effectively for a disease other than what it’s prescribed for. Usually, programs like Medicare will cover certain off-label use, but you’ll have to check with your insurance.
If insurance is not paying for the immunotherapy drug, then it will be out of pocket and can be costly. In the tens of thousands to hundreds of thousands of dollars. There are ways to outreach to the drug manufacturer and ask for the drug based on compassion (known as “compassionate use”). My own doctors recommended this to me if we needed to go down the road of immunotherapy since my cancer is rare and surprise, was not on the approved list (so far we have not had to do that).
I also would not qualify for some clinical trials, considering my neutrophil count is too low (which is sometimes a requirement) and my tumor had mixed histology (it was both small cell neuroendocrine and adenocarcinoma).
As you can imagine, navigating compassionate use and hunting down clinical trials you actually qualify for can be overwhelming. I encourage people to use resources available at places like the Cancer Research Institute, who graciously answered my questions about immunotherapy in their effort to bring more resources to cancer patients.
When Immunotherapy hit the cancer world it was a game-changer, for a small number of cancer patients. Hopefully, the science will continue to expand and the rate of success can increase.
As Dr. Fecci explained, “Immunotherapy remains one of the most (if not THE most) promising and exciting anti-cancer modality presently.” Adding that it’s especially prevalent for melanoma and lung cancers of certain types, with expanding uses in breast, kidney, and GI cancers (of certain types).
Of course, the real goal of immunotherapy is to expand its access and its efficacy to give hope to more patients. “A key to unlocking broader success amongst greater numbers or patients and greater numbers of cancers will, I believe, be found in analyzing the various differences between people and tumors that respond very very well to these therapies, and those that respond less well,” says Dr. Fecci.
Once those differences are better understood, it could lead to a revolution in cancer care.